The long-term objective of this program is to understand the mechanism(s) of neoplastic transformation in cultured mammalian cells, particularly human cells. Studies described address two intermediate goals: (a) the role of calcium and dissolved oxygen on survival, proliferation, and differentiated function; and (b) the induction of cellular injury after cell exposure to low-intensity visible light. In studies to date, a lowered calcium concentration appears to retard differentiation of human epithelial cells in that squame formation is not observed; unlike the mouse epithelial system, however, proliferation is not enhanced by lowering calcium concentration. In addition, human skin and monkey kidney cells exhibit a critical oxygen requirement for attachment and proliferation, and monkey kidney cells use oxygen more rapidly than fibroblasts at the same cell density. This rapid utilization affects proliferation and functional responses. Visible light causes chromatid damage in normal human fibroblasts. A medium-specific, cell-type specific cell killing is observed when fibroblasts are exposed to light in medium NCTC 168, a response mediated by hydrogen peroxide products during light exposure.